High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in Malawi

Montgomery, Nathan D.; Randall, Cara; Painschab, Matthew; Séguin, Ryan; Kaimila, Bongani; Kasonkanji, Edwards; Zuze, Takondwa; Krysiak, Robert; Sanders, Marcia K.; Avian, Elliott,; Miller, Melissa B.; Kampani, Coxcilly; Chimzimu, Fred; Mulenga, Maurice; Damania, Blossom; Tomoka, Tamiwe; Fedoriw, Yuri; Dittmer, Dirk P.; Gopal, Satish

doi:10.1002/cam4.2710

Cited by 13 publications

(16 citation statements)

References 46 publications

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“…1,11,[19][20][21] Montgomery et al confirmed that high plasma pre-EBV DNA was an adverse prognostic marker for DLBCL patients. 22 But circulating tumor cells or other EBV-infected cells should also be considered to reflect the patient's EBV DNA load. Therefore, we analyzed the differential expression of whole blood EBV DNA in lymphomas and its relationship with prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…EBV DNA load is highly correlated with the prognosis of types of lymphoma. [22][23][24][25] Previous study has shown that among NKTL patients who received L-asparaginase-based SMILE regimen, those with a higher EBV DNA load also had a poorer prognosis. 26 Our study had shown that there were disparities in whole blood EBV DNA loads among different lymphomas.…”

Section: Discussionmentioning

confidence: 99%

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Disparity analysis and prognostic value of pretreatment whole blood Epstein‐Barr virus DNA load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Shen

Yao

et al. 2021

Intl Journal of Cancer

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Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disparity analysis and prognostic value of pretreatment whole blood Epstein‐Barr virus DNA load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Shen

Yao

et al. 2021

Intl Journal of Cancer

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“…Fewer studies have been performed measuring EBV in peripheral blood of PLWH to determine its value as a diagnostic tool and prognostic factor. In this regard, the detection of EBV load has been reported to be more frequent among lymphomas in PLWH than in the general population [ 25 , 208 , 209 ]. Moreover, some studies, including ours, have suggested that EBV load measured in plasma could be a useful tool for the diagnosis of NHL and HL in PLWH, since EBV has been detected in plasma of these patients at lymphoma diagnosis [ 210 , 211 ].…”

Section: Implications Of Ebv Load In Hiv-related Lymphomamentioning

confidence: 99%

“…Some studies have pointed out that the presence of EBV in peripheral blood could be used as a prognostic factor in HRL. Individuals with high levels of EBV load in plasma have shown worse OS [ 25 , 209 , 210 , 211 ]. In this regard, Muncunill et al reported a negative impact of high EBV load on the survival of HIV-related NHL treated without rituximab.…”

Section: Implications Of Ebv Load In Hiv-related Lymphomamentioning

confidence: 99%

Clinical and Therapeutic Implications of Epstein–Barr Virus in HIV-Related Lymphomas

Verdu-Bou

Tapia

Hernández-Rodríguez

et al. 2021

Cancers

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The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein–Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV and EBV can lead to the proliferation of aberrant B-cells, thereby being an additional lymphomagenic mechanism in EBV-associated HRL. Despite the close relationship between EBV and HRL, the impact of EBV on clinical aspects has not been extensively studied. These lymphomas are treated with the same therapeutic regimens as the general population in combination with cART. Nevertheless, new therapeutic strategies targeting EBV are promising for these lymphomas. In this article, the different types of HRL are extensively reviewed, focusing on the influence of EBV on the epidemiology, pathogenesis, clinical presentation, and pathological characteristics of each lymphoma subtype. Moreover, novel therapies targeting EBV and future strategies to treat HRL harboring EBV are discussed.

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“…The impact of HIV infection on the disease incidence of EBV-associated LPDs is less clear. High plasma EBV DNA level was identified as a poor prognostic factor associated with reduced OS in HIV-associated, EBV-negative DLBCL in Malawi ( 188 ). However, diagnosis of EBV-association via in-situ-hybridization for EBER is not a common practice in most countries in the Africa continent and there is a limitation on the cancer registry data.…”

Section: Hiv and Ebv+ Lymphomas In Sub-saharan Africamentioning

confidence: 99%

Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals

et al. 2020

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Epstein-Bar virus (EBV) can directly cause lymphoproliferative disease (LPD), including AIDS-defining lymphomas such as Burkitt's lymphoma and other non-Hodgkin lymphomas (NHL), as well as human immunodeficiency virus (HIV)-related Hodgkin lymphoma (HL). The prevalence of EBV in HL and NHL is elevated in HIV-positive individuals compared with the general population. Rates of incidence of AIDS-defining cancers have been declining in HIV-infected individuals since initiation of combination anti-retroviral therapy (cART) use in 1996. However, HIV-infected persons remain at an increased risk of cancers related to infections with oncogenic viruses. Proposed pathogenic mechanisms of HIV-related cancers include decreased immune surveillance, decreased ability to suppress infection-related oncogenic processes and a state of chronic inflammation marked by alteration of the cytokine profile and expanded numbers of cytotoxic T lymphocytes with down-regulated co-stimulatory molecules and increased expression of markers of senescence in the setting of treated HIV infection. Here we discuss the cooperation of EBV-infected B cell-and environment-associated factors that may contribute to EBV-related lymphomagenesis in HIV-infected individuals. Environment-derived lymphomagenic factors include impaired host adaptive and innate immune surveillance, cytokine dysregulation and a pro-inflammatory state observed in the setting of chronic, cART-treated HIV infection. B cell factors include distinctive EBV latency patterns and host protein expression in HIV-associated LPD, as well as B cell-stimulating factors derived from HIV infection. We review the future directions for expanding therapeutic approaches in targeting the viral and immune components of EBV LPD pathogenesis.

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High pretreatment plasma Epstein‐Barr virus (EBV) DNA level is a poor prognostic marker in HIV‐associated, EBV‐negative diffuse large B‐cell lymphoma in Malawi

Abstract: Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker.

Cited by 13 publications

References 46 publications

Disparity analysis and prognostic value of pretreatment whole blood Epstein‐Barr virus DNA load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Disparity analysis and prognostic value of pretreatment whole blood Epstein‐Barr virus DNA load and Epstein‐Barr encoding region status in lymphomas: A retrospective multicenter study in Huaihai Lymphoma Working Group

Clinical and Therapeutic Implications of Epstein–Barr Virus in HIV-Related Lymphomas

Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals

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